{
  "abstract": "Ataxia–telangiectasia mutated (ATM) is a central regulator of the DNA damage response (DDR), coordinating DNA double-strand break signaling, checkpoint activation, and maintenance of genome stability. Although traditionally regarded as a tumor suppressor, accumulating evidence indicates that many established cancers become functionally dependent on residual ATM signaling to tolerate oncogene-driven replication stress, genomic instability, oxidative stress, and defective checkpoint control. This context-dependent reliance reflects a form of non-oncogene addiction in which ATM signaling is selectively retained to sustain tumor cell survival, particularly in TP53-deficient and highly replication-stressed malignancies. Beyond canonical DDR functions, ATM also contributes to tumor progression through regulation of NF-κB signaling, epithelial–mesenchymal transition, hypoxia adaptation, metabolic rewiring, mitochondrial homeostasis, and immune modulation. These diverse activities provide a strong rationale for therapeutic ATM inhibition. Pharmacological ATM inhibitors impair checkpoint signaling and DNA repair, thereby sensitizing tumors to radiotherapy and DNA-damaging agents and promoting synthetic lethal interactions in DDR-deficient backgrounds. In this review, we aim to integrate current mechanistic, preclinical, and translational evidence linking ATM biology with the pharmacological and clinical development of small-molecule inhibitors, including KU-55933, KU-59403, KU-60019, CP466722, WSD0628, AZD0156, AZD1390, M3541, SYH2051, and XRD-0394. We further discuss emerging concepts such as context-specific synthetic vulnerabilities, radio-immunotherapy combinations, pharmacokinetic and toxicity considerations, mechanisms of resistance, and the limitations of current preclinical models. Collectively, ATM inhibition represents a promising precision oncology strategy for exploiting DDR dependencies and overcoming therapeutic resistance in genetically unstable cancers.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Molecular Biotechnology and Genetics, University of Lodz, Lodz, Poland",
    "Department of Functional Genomics, Faculty of Medicine, Medical University of Lodz, Lodz, Poland",
    "BioMedChem Doctoral School of the University of Lodz and Lodz Institutes of the Polish Academy of Sciences, Lodz, Poland",
    "Department of Inorganic and Analytical Chemistry, University of Lodz, Lodz, Poland",
    "Doctoral School of Exact and Natural Sciences, University of Lodz, Lodz, Poland",
    "Doctoral School of Molecular Medicine, Medical University of Lodz, Lodz, Poland"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Mateusz Kciuk",
      "orcid": "0000-0002-8616-3825"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Gabriela Machura",
      "orcid": "0009-0003-4018-8570"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Katarzyna Wanke"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Piotr Gromek",
      "orcid": "0009-0005-8093-8481"
    },
    {
      "affs": [
        0
      ],
      "name": "Beata Marciniak",
      "orcid": "0000-0001-8109-6478"
    },
    {
      "affs": [
        0
      ],
      "name": "Renata Kontek",
      "orcid": "0000-0003-2859-9839"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/abbqffprew2fs.bib",
  "cited_by": 0,
  "doi": "10.32604/or.2026.082180",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732375/",
  "id": "abbqffprew2fs",
  "issns": [
    "0965-0407",
    "1555-3906"
  ],
  "landing_url": "https://doi.org/10.32604/or.2026.082180",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Review"
    ],
    [
      "openalex",
      "1312|DNA Repair Mechanisms"
    ]
  ],
  "openalex": "W7164829324",
  "pdf_url": null,
  "pmcid": "PMC13732375",
  "pmid": "42984918",
  "published": "2026-10-28",
  "publisher": "Tech Science Press",
  "ris": "https://research.draconitic.com/paper/abbqffprew2fs.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:22Z",
      "native_id": "PMC13732375",
      "source": "pmc",
      "url": "https://doi.org/10.32604/or.2026.082180"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|DNA Repair Mechanisms",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Targeting ATM Kinase in Cancer—A Comprehensive Review",
  "title_text": "Targeting ATM Kinase in Cancer—A Comprehensive Review",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:22Z",
  "url": "https://research.draconitic.com/paper/abbqffprew2fs",
  "venue": "Oncology Research",
  "versions": []
}